This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The key to understanding the results of the STEP/Phambili trials is first to model the results of the trial in controlled experiments using mucosal SIV inoculation of rhesus macaques. Thus, we will determine the effectiveness and potential of the Merck trivalent HIV adenovirus 5 vector vaccine (V520) for enhancing susceptibility to S1V in a rhesus macaque model of mucosal HIV transmission. If models of vaccine protection or enhancement are established, the immune mechanisms and inflammation/activation associated with any protective or enhancing effects can be defined in a renewal application.